Record Information
Version2.0
Creation Date2009-03-06 11:58:01 -0700
Update Date2014-11-04 15:48:35 -0700
Accession NumberT3D0064
Identification
Common Nametrans-Chlordane
ClassSmall Molecule
DescriptionTrans-chlordane, also known as gamma-chlordane, is one of two isomers of chlordane. Chlordane is a manufactured chemical that was used as a pesticide in the United States from 1948 to 1988. (9)
Compound Type
  • Organic Compound
  • Organochloride
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
b-Chlordan
b-Chlordane
Beta-chlordane
Chlordane gamma
Chlordane trans
Trans-(gamma)-chlordane
trans-Chlordan
Trans-gamma-chlordane
Chemical FormulaC10H6Cl8
Average Molecular Mass409.779 g/mol
Monoisotopic Mass405.798 g/mol
CAS Registry Number5103-74-2
IUPAC Name(1R,3R,4R,7S)-1,3,4,7,8,9,10,10-octachlorotricyclo[5.2.1.0²,⁶]dec-8-ene
Traditional Name(1R,3R,4R,7S)-1,3,4,7,8,9,10,10-octachlorotricyclo[5.2.1.0²,⁶]dec-8-ene
SMILES[H][C@@]1(Cl)CC2([H])C([H])([C@@]1([H])Cl)[C@@]1(Cl)C(Cl)=C(Cl)[C@]2(Cl)C1(Cl)Cl
InChI IdentifierInChI=1S/C10H6Cl8/c11-3-1-2-4(5(3)12)9(16)7(14)6(13)8(2,15)10(9,17)18/h2-5H,1H2/t2?,3-,4?,5+,8+,9-/m1/s1
InChI KeyInChIKey=BIWJNBZANLAXMG-MRTOWHRVSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassOrganohalogen Compounds
ClassVinyl Halides
Sub ClassVinyl Chlorides
Direct ParentVinyl Chlorides
Alternative Parents
Substituents
  • Organochloride
  • Alkyl Chloride
  • Alkyl Halide
  • Aliphatic Homopolycyclic Compound
  • Chloroalkene
  • Vinyl Chloride
  • Haloalkene
Molecular FrameworkAliphatic Homopolycyclic Compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cell junction
  • Extracellular
  • Membrane
  • Mitochondrion
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Degradation Of Aromatic CompoundsNot AvailableNot Available
EicosanoidsNot AvailableNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceColorless to amber liquid.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility5.6e-05 mg/mL at 25 °C [MABEY,WR et al. (1981)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility6.89e-05ALOGPS
logP6.02ALOGPS
logP5.27ChemAxon
logS-6.8ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity80.38 m3·mol-1ChemAxon
Polarizability32.63 Å3ChemAxon
Spectra
SpectraNot Available
Toxicity Profile
Route of ExposureOral (5) ; inhalation (5)
Mechanism of ToxicityChlordane is believed to bind irreversibly to DNA, leading to cell death or altered cellular function. It also affects transcription by antagonizing estrogen-related receptors. Chlordane induces hepatic cytochrome P-450, causing a large increase in the volume of the smooth endoplasmic reticulum, which results in hepatocellular enlargement and hypertrophy. Chlordane has also been shown to bind and activate retinoic acid receptor, causing various developmental defects, and inhibit alkaline phosphatases in hepatic and renal tissues. (10, 1, 2, 3, 4)
MetabolismChlordane is highly lipophilic and is thus easily absorbed by ingestion, inhalation, and dermal exposure, then stored mainly in the fat. Chlordane is metabolized mainly in the liver and kidney. Metabolism is slow, and is believed to occur by multiple pathways involving cytochrome P-450 enzymes, glutathione-S-transferase type enzymes, and microsomal mixed-function oxidase systems. The metabolites are generally less toxic and include chlordene chlorohydrin, monohydroxylated dihydrochlordene, and oxychlordane. They are excreted in the urine and faeces. (10)
Toxicity ValuesLD50: 200 mg/kg (Oral, Rat) (6) LD50: 343 mg/kg (Intraperitoneal, Rat) (6) LD50: 10 mg/kg (Intravenous, Mouse) (7) LD50: 780 mg/kg (Dermal, Rat) (7) LC50: 100 mg/m3 over 4 hours (Inhalation, Cat) (7)
Lethal Dose100 mg/kg for an adult human. (8)
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (12)
Uses/SourcesChlordane was used as a pesticide. (9)
Minimum Risk LevelIntermediate Inhalation: 0.0002 mg/m3 (11) Chronic Inhalation: 0.00002 mg/m3 (11) Acute Oral: 0.001 mg/kg/day (11) Intermediate Oral: 0.0006 mg/kg/day (11) Chronic Oral: 0.0006 mg/kg/day (11)
Health EffectsChlordane is a central nervous system stimulant, and can also damage the digestive system and the liver. Large doses have been shown to cause convulsions, respiratory failure, and death. Chlordane is also known to have adverse reproductive and developmental effects. (10)
SymptomsIngestion and inhalation of chlordane cause headaches, irritability, confusion, weakness, vision problems, vomiting, stomach cramps, diarrhea, and jaundice. (10)
TreatmentTreatment is symptomatic. It is aimed at controlling convulsions, coma, and respiratory depression. Gastric lavage, followed by the administration of activated charcoal, may be performed following ingestion. (13)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID12303020
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID39069
BioCyc IDNot Available
CTD IDNot Available
Stitch IDChlordane, trans-
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D0064.pdf
General References
  1. Ariazi EA, Jordan VC: Estrogen-related receptors as emerging targets in cancer and metabolic disorders. Curr Top Med Chem. 2006;6(3):203-15. [16515477 ]
  2. Lemaire G, Balaguer P, Michel S, Rahmani R: Activation of retinoic acid receptor-dependent transcription by organochlorine pesticides. Toxicol Appl Pharmacol. 2005 Jan 1;202(1):38-49. [15589975 ]
  3. Nims RW, Lubet RA: Induction of cytochrome P-450 in the Norway rat, Rattus norvegicus, following exposure to potential environmental contaminants. J Toxicol Environ Health. 1995 Nov;46(3):271-92. [7473857 ]
  4. Chatterjee K, Banerjee SK, Tiwari R, Mazumdar K, Bhattacharyya A, Chatterjee GC: Studies on the protective effects of L-ascorbic acid in chronic chlordane toxicity. Int J Vitam Nutr Res. 1981;51(3):254-65. [7319725 ]
  5. Melnick RL, Schiller CM: Mitochondrial toxicity of phthalate esters. Environ Health Perspect. 1982 Nov;45:51-6. [7140696 ]
  6. Lewis RJ Sr. (ed) (2004). Sax's Dangerous Properties of Industrial Materials. 11th Edition. Hoboken, NJ: Wiley-Interscience, Wiley & Sons, Inc.
  7. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  8. US Environmental Protection Agency (2001). OHM/TADS: Oil and Hazardous Materials/Technical Assistance Data System. Washington, DC (Internet Version). Edition expires 2001. Greenwood Village, CO: Thomson Healthcare Inc.
  9. Wikipedia. Chlordane. Last Updated 2 April 2009. [Link]
  10. ATSDR - Agency for Toxic Substances and Disease Registry (1994). Toxicological profile for chlordane. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  11. ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  12. International Agency for Research on Cancer (2009). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  13. International Programme on Chemical Safety (IPCS) INCHEM (2000). Poison Information Monograph for Chlordane. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Secondary metabolites biosynthesis, transport and catabolism
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular Weight:
56277.8 Da
References
  1. Nims RW, Lubet RA: Induction of cytochrome P-450 in the Norway rat, Rattus norvegicus, following exposure to potential environmental contaminants. J Toxicol Environ Health. 1995 Nov;46(3):271-92. [7473857 ]
  2. ATSDR - Agency for Toxic Substances and Disease Registry (1994). Toxicological profile for chlordane. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Involved in monooxygenase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57344.0 Da
References
  1. Nims RW, Lubet RA: Induction of cytochrome P-450 in the Norway rat, Rattus norvegicus, following exposure to potential environmental contaminants. J Toxicol Environ Health. 1995 Nov;46(3):271-92. [7473857 ]
  2. ATSDR - Agency for Toxic Substances and Disease Registry (1994). Toxicological profile for chlordane. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Secondary metabolites biosynthesis, transport and catabolism
Specific Function:
Exhibits low testosterone 6-beta-hydroxylase activity
Gene Name:
CYP3A43
Uniprot ID:
Q9HB55
Molecular Weight:
57669.2 Da
References
  1. Nims RW, Lubet RA: Induction of cytochrome P-450 in the Norway rat, Rattus norvegicus, following exposure to potential environmental contaminants. J Toxicol Environ Health. 1995 Nov;46(3):271-92. [7473857 ]
  2. ATSDR - Agency for Toxic Substances and Disease Registry (1994). Toxicological profile for chlordane. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Secondary metabolites biosynthesis, transport and catabolism
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57109.0 Da
References
  1. Nims RW, Lubet RA: Induction of cytochrome P-450 in the Norway rat, Rattus norvegicus, following exposure to potential environmental contaminants. J Toxicol Environ Health. 1995 Nov;46(3):271-92. [7473857 ]
  2. ATSDR - Agency for Toxic Substances and Disease Registry (1994). Toxicological profile for chlordane. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Secondary metabolites biosynthesis, transport and catabolism
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular Weight:
57525.0 Da
References
  1. Nims RW, Lubet RA: Induction of cytochrome P-450 in the Norway rat, Rattus norvegicus, following exposure to potential environmental contaminants. J Toxicol Environ Health. 1995 Nov;46(3):271-92. [7473857 ]
  2. ATSDR - Agency for Toxic Substances and Disease Registry (1994). Toxicological profile for chlordane. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Involved in transcription factor activity
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66217.0 Da
References
  1. Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
  2. Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
General Function:
Involved in transcription factor activity
Specific Function:
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA- binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59217.0 Da
References
  1. Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
  2. Luft S, Milki E, Glustrom E, Ampiah-Bonney R, O'Hara P. Binding of Organochloride and Pyrethroid Pesticides To Estrogen Receptors α and β: A Fluorescence Polarization Assay. Biophysical Journal 2009;96(3):444a.
General Function:
Inorganic ion transport and metabolism
Specific Function:
This isozyme may play a role in skeletal mineralization
Gene Name:
ALPL
Uniprot ID:
P05186
Molecular Weight:
57304.4 Da
References
  1. Chatterjee K, Banerjee SK, Tiwari R, Mazumdar K, Bhattacharyya A, Chatterjee GC: Studies on the protective effects of L-ascorbic acid in chronic chlordane toxicity. Int J Vitam Nutr Res. 1981;51(3):254-65. [7319725 ]
9. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (1994). Toxicological profile for chlordane. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
General Function:
Not Available
Specific Function:
Orphan receptor. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements
Gene Name:
ESRRG
Uniprot ID:
P62508
Molecular Weight:
51307.0 Da
References
  1. Ariazi EA, Jordan VC: Estrogen-related receptors as emerging targets in cancer and metabolic disorders. Curr Top Med Chem. 2006;6(3):203-15. [16515477 ]
General Function:
Involved in transcription factor activity
Specific Function:
This is a receptor for retinoic acid. This metabolite has profound effects on vertebrate development. Retinoic acid is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression
Gene Name:
RARB
Uniprot ID:
P10826
Molecular Weight:
50490.0 Da
References
  1. Lemaire G, Balaguer P, Michel S, Rahmani R: Activation of retinoic acid receptor-dependent transcription by organochlorine pesticides. Toxicol Appl Pharmacol. 2005 Jan 1;202(1):38-49. [15589975 ]
General Function:
Involved in transcription factor activity
Specific Function:
This is a receptor for retinoic acid. This metabolite has profound effects on vertebrate development. Retinoic acid is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression
Gene Name:
RARG
Uniprot ID:
P13631
Molecular Weight:
50342.0 Da
References
  1. Lemaire G, Balaguer P, Michel S, Rahmani R: Activation of retinoic acid receptor-dependent transcription by organochlorine pesticides. Toxicol Appl Pharmacol. 2005 Jan 1;202(1):38-49. [15589975 ]
General Function:
Involved in protein domain specific binding
Specific Function:
Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism
Gene Name:
ESRRA
Uniprot ID:
P11474
Molecular Weight:
45509.1 Da
References
  1. Ariazi EA, Jordan VC: Estrogen-related receptors as emerging targets in cancer and metabolic disorders. Curr Top Med Chem. 2006;6(3):203-15. [16515477 ]
General Function:
Involved in trophectodermal cellular morphogenesis
Specific Function:
Nuclear receptor, may regulate ESR1 transcriptional activity. Induces the expression of PERM1 in the skeletal muscle.
Gene Name:
ESRRB
Uniprot ID:
O95718
Molecular Weight:
56207.085 Da
References
  1. Ariazi EA, Jordan VC: Estrogen-related receptors as emerging targets in cancer and metabolic disorders. Curr Top Med Chem. 2006;6(3):203-15. [16515477 ]